Birth weight and perfluorooctane sulfonic acid: a random-effects meta-regression analysis

Abstract

Background: Perfluorooctane sulfonic acid (PFOS) is a ubiquitous environmental contaminant. Most people in developed countries have detectable serum concentrations. Lower birth weight has been associated with serum PFOS in studies world-wide, many of which have been published only recently. Methods: To facilitate a causal assessment of the birth weight and PFOS association, we updated previous meta-analyses of the association and employed a method that facilitated inclusion of all available data in one analysis. Our analysis was based on observations from 29 studies. Results: The random effects summary was −3.22 g/ng/ml (95% confidence interval [CI] = −5.11, −1.33). In a subgroup analysis stratified by when in pregnancy the PFOS concentration was measured, the summary for the early group was −1.35 (95% CI = −2.33, −0.37) and for the later group was −7.17 (95% CI = −10.93, −3.41). In a meta-regression model including a term for timing of blood draw, the intercept was slightly positive but essentially zero (0.59 g/ng/ml, 95% CI = −1.94, 3.11). In other words, the model indicated that when blood was drawn at the very beginning of pregnancy, there was essentially no relation of birth weight to PFOS. The results from the subgroup analyses differed from those from the model because the average gestational age at blood draw in the early group was 14 weeks, when bias would still be expected. A stronger inverse association in Asian studies was not completely explained by their blood draws being from later in pregnancy. Conclusions: The evidence was weakly or not supportive of a causal association.

Association Between Exposure to Per- and Polyfluoroalkyl Substances and Birth Outcomes: A Systematic Review and Meta-Analysis

“…Maximally adjusted effect estimates (regression coefficients, ORs, and RRs) were additionally extracted wherever possible. When the effect estimates for the total population are not available, for example, in studies ( 39 – 41 ) that showed the data for males and females separately, we treated them as separately studies as described by Negri et al ( 47 ) and Dzierlenga et al ( 49 ). We also did the same with Lauritzen et al ( 63 ), which included two cohorts (Norway and Sweden).…”

“…In addition, some studies ( 39 – 41 ) revealed that differences in fetal sex and gestational order may influence the exposure and birth outcome associations, while others ( 12 , 29 , 42 – 45 ) discussed the time-course variation in the timing of PFAS collection vs. exposure measurement. Although some epidemiological studies have been conducted to explore the associations, the conclusions of this evidence are quite inconsistent or even opposite ( 12 , 13 , 20 , 38 , 46 , 47 ), even if studies ( 48 , 49 ) focus on only one outcome indicator (e.g., BW). Such inconsistency may be related to the degree of adjustment for confounding factors, the difference in study design and population characteristics, and the difference in ways of data units and transformations.…”

High in Utero Exposure to Perfluoroalkyl Substances from Drinking Water and Birth Weight: A Cohort Study among Infants in Ronneby, Sweden

“…Although the exposure range between referents with background exposure and Ronneby high exposure is known to be large, the differences in birth weight between those groups were only around 50 g. Since previous studies have shown that individuals with high exposure in Ronneby have average levels of PFOS of around 200 ng/mL, and women of fertile age had approximately half of these average levels [ 39 ], the changes in birth weights seen in our study give us rough estimates of around −0.50 g (boys) and +0.50 g (girls) change per ng/mL increase in serum PFOS, respectively. Previous meta-analyses of epidemiologic studies have suggested that each nanogram per milliliter increase in maternal serum PFOS concentrations was associated with reductions in birth weight of −0.92 g (95% CI −3.4; 1.6) [ 46 ] and −3.22 g/ng/mL (95% CI −5.11, −1.33) [ 47 ]. There is a complexity in evaluating associations between maternal serum during pregnancy and birth weight: a previous meta-analysis [ 48 ] showed that when a term for the timing of blood draw was included in the model, there was essentially no relationship between birth weight and PFOS, and when using serum sampled early in pregnancy, little or no association was found between PFOA and birth weight.…”

Re-expressing coefficients from regression models for inclusion in a meta-analysis

“…The Dzierlenga et al ( 2020) algorithm ("Dz estimator") for re-expression [8] was described in the introduction above. We note that this method can handle multiple different measures of exposure central tendency and spread such that when medians and quartiles were not available, but geometric or arithmetic means and standard deviations were, the algorithm will accept those as inputs.…”

“…They recommended caution in applying their method when the distribution of the independent variable was markedly asymmetric. More recently, empiric methods of re-expressing coefficients from models fit to a log-transformed independent variable to approximate what would have been obtained if fit to an original unit continuous independent exposure have been presented [7,8]. Steenland et al (2018) described their method as … iteratively minimizing the squared deviation of a new linear curve from the original logarithmic one, over a scale of 0 to 10 ng/ml PFOA [perfluorooctanoic acid], typical of studies in the general population.…”